Interhelical interactions between D92 and C218 in the cytoplasmic domain regulate proton uptake upon N-decay in the proton transport of Acetabularia rhodopsin II.

Acetabularia rhodopsin II (ARII or Ace2), an outward light-driven algal proton pump found in the giant unicellular marine alga Acetabularia acetabulum, has a unique property in the cytoplasmic (CP) side of its channel. The X-ray crystal structure of ARII in a dark state suggested the formation of an interhelical hydrogen bond between C218ARII and D92ARII, an internal proton donor to the Schiff base (Wada et al., 2011). In this report, we investigated the photocycles of two mutants at position C218ARII: C218AARII which disrupts the interaction with D92ARII, and C218SARII which potentially forms a stronger hydrogen bond. Both mutants exhibited slower photocycles compared to the wild-type pump. Together with several kinetic changes of the photoproducts in the first half of the photocycle, these replacements led to specific retardation of the N-to-O transition in the second half of the photocycle. In addition, measurements of the flash-induced proton uptake and release using a pH-sensitive indium-tin oxide electrode revealed a concomitant delay in the proton uptake. These observations strongly suggest the importance of a native weak hydrogen bond between C218ARII and D92ARII for proper proton translocation in the CP channel during N-decay. A putative role for the D92ARII-C218ARII interhelical hydrogen bond in the function of ARII is discussed.

Four-year clinical outcomes of the OLIVUS-Ex (impact of Olmesartan on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) extension trial.

BACKGROUND: The previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with olmesartan. METHODS: Serial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20-40mg of olmesartan or control, and treated with a combination of ß-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE). RESULTS: Cumulative event-free survival was significantly higher in the olmesartan group than in the control group (p=0.04; log-rank test). By adjusting for validated prognosticators, olmesartan administration was identified as a good predictor of MACCE (p=0.041). On the other hand, patients with adverse events (n=31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p<0.001). CONCLUSIONS: Olmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.

Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial.

OBJECTIVES: The aim of this study was to evaluate the impact of olmesartan on progression of coronary atherosclerosis. BACKGROUND: Prior intravascular ultrasound (IVUS) trial results suggest slowing of coronary atheroma progression with some medicines but have not shown convincing evidence of regression with angiotension-II receptor blocking agents. METHODS: A prospective, randomized, multicenter trial-OLIVUS (Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound)-was performed in 247 stable angina pectoris patients with native coronary artery disease. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their nonculprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 10 to 40 mg of olmesartan or control and treated with a combination of beta-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents, and/or statins per physician's guidance. Serial IVUS examinations (baseline and 14-month follow-up) were performed to assess coronary atheroma volume. Volumetric IVUS analyses included lumen, plaque, vessel volume, percent atheroma volume (PAV), percent change in total atheroma volume (TAV) and PAV. RESULTS: Patient characteristics and blood pressure control were identical between the 2 groups. However, follow-up IVUS showed significantly decreased TAV and percent change in PAV in the olmesartan group (5.4% vs. 0.6 % for TAV and 3.1% vs. -0.7% for percent change in PAV, control vs. olmesartan, p < 0.05 for all). CONCLUSIONS: These observations suggest a positive role in a potentially lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.

Torsade de pointes associated with bradycardia and takotsubo cardiomyopathy.

Two cases of torsade de pointes associated with bradycardia and takotsubo cardiomyopathy are reported. In both cases, atrioventricular block preceded the occurrence of takotsubo cardiomyopathy. Bradycardia-induced QT interval prolongation seemed to be amplified by the occurrence of takotsubo cardiomyopathy, resulting in torsade de pointes. Temporary ventricular pacing at a high rate decreased the QT interval and prevented the recurrence of torsade de pointes. Because atrioventricular block recurred or persisted even after the resolution of takotsubo cardiomyopathy, the patients received permanent pacemakers.

Variant form of tako-tsubo cardiomyopathy.

We report a female case of variant form of tako-tsubo cardiomyopathy in which wall motion of the distal segment was preserved. In the current case, left ventriculography showed akinesia of the mid portion and normokinesia of the distal and basal portions of the left ventricular chamber. ST-segment elevation was obvious in leads V1-3 rather than in leads V4-6. Because ST-segment elevation is absent in left precordial leads, cardiologists should take care not to fail to diagnose variant form of tako-tsubo cardiomyopathy.

Tako-tsubo cardiomyopathy after automobile accident.

A 53-year-old woman was involved in a traffic accident while driving her car. She had chest oppressive sensation 6 h after the accident, and was admitted to our hospital. On admission, she had no external injury. She was fully conscious, and felt anxiety about the accident. Twelve-lead electrocardiogram showed mild ST-segment elevation in leads II, III, aVF and V2-5. Chest X-ray did not show pneumothorax, rib fracture or pulmonary congestion. Emergency coronary angiography showed no significant coronary artery disease. However, left ventriculography showed akinesia of the mid-to-distal portion of the left ventricular chamber and hyperkinesia of the basal portion (ejection fraction=45%). She was diagnosed as having tako-tsubo cardiomyopathy. Follow-up left ventriculography 11 days later showed normal wall motion of the left ventricular chamber (ejection fraction=62%). Clinicians should recognize that tako-tsubo cardiomyopathy is one of etiologies of chest symptom after automobile accident. It can occur due to emotional stress even if patients have no external injury.

Documentation of early improvement of left ventricular function in tako-tsubo cardiomyopathy.

An 86-year-old woman was admitted to our hospital because of chest pain after a heated argument with her daughter. Electrocardiogram showed ST-segment elevation in leads V2-3 and T wave inversion in leads V3-6. Emergency cardiac catheterization was performed 2 h after the onset of chest pain. Coronary angiography showed no significant coronary artery disease. However, left ventriculography showed apical akinesis and basal hyperkinesis (ejection fraction=42%). She was diagnosed as having tako-tsubo cardiomyopathy. Follow-up left ventriculography showed marked improvement of the left ventricular function (ejection fraction=74%) during only 41 h. She was discharged 3 days later.